Sulfate conjugation is an important pathway in the biotransformation of many neurotransmitters, hormones, drugs and other xenobiotics, and is catalyzed by cytosolic sulfotransferase enzymes designated “SULT.” SULT enzymes are encoded by a gene superfamily, which, in mammals, is divided into two families, SULT1 or phenol SULTs and SULT2 or hydroxysteroid SULTs. The SULT1 and SULT2 families share at least 45% amino acid sequence identity, while members of subfamilies within each family share at least 60% amino acid sequence identity. SULT1 subfamilies include the phenol (1A), thyroid hormone (1B), hydroxyarylamine (1C), and estrogen (1E) subfamilies. SULT2 subfamilies include two hydroxysteroid SULTs, 2A1 and 2B1.
Members of the SULT1C subfamily, including SULT1C1 and SULT1C2, catalyze the sulfate conjugation of thyroid hormones and carcinogenic hydroxyarylamines. A human SULT1C1 cDNA, which was cloned from a fetal liver-spleen cDNA library, encodes a protein that is 62% identical to the amino acid sequence of a rat SULT designated “ST1C1”. Her et al., Genomics (1997) 41: 467–470. ST1C1 catalyzes the metabolic activation of the procarcinogen N-hydroxy-2-acetylaminofluorene. The amino acid sequences of human SULT1C1 and human SULT1C2 are 62.6% identical. Sakakibara et al., J. Biol. Chem. (1998) 273:33929–33935. Human SULT1C1 is highly expressed in stomach, kidney, liver, and thyroid, while SULT1C2 is highly expressed in fetal lung and fetal kidney.